In order to understand genetic basis underlying complex traits, such as morphology and energy metabolism, we are conducting genetic analyses based upon both of “Forward Genetics” using existing mouse mutants and “Reverse Genetics” using genetically engineered mice. In parallel, we are also compiling information of the genome diversity of inbred mouse strains, and developing new inter-subspecific consomic strains, in which every chromosome of a classical inbred strain C57BL/6J is replaced by the counterpart of a wild mouse-derived MSM/Ms strain. These bioresources are freely available for research community.
Shh enhancer evolution:
MACS1 is a Shh endoderm enhancer that emerged prior to the divergence of cartilaginous and bony fishes. Ray-finned fishes evolved a novel conserved non-coding sequence named Block-2. The MACS1 activity in the ventral digestive tube has been lost in the euteleost lineage, and Block-2 acquired an enhancer activity for dorsal epithelial expression in the digestive tube. It implicates that evolution of these two enhancers is relevant to the morphological transition from ventral lungs to dorsal gasbladder.
Sagai, T., Amano, T., Maeno, A., Kimura, T., Nakamoto, M., Takehana, Y., Naruse, K., Okada, N., Kiyonari, H., and Shiroishi, T. (2017). Evolution of Shh endoderm enhancers during morphological transition from ventral lungs to dorsal gas bladder. Nat commun 8, 14300.
Takada, T., Yoshiki, A., Obata, Y., Yamazaki, Y., and Shiroishi, T. (2015). NIG_MoG: a mouse genome navigator for exploring intersubspecific genetic polymorphisms. Mamm Genome 26, 331-337.
Oka, A., Takada, T., Fujisawa, H., and Shiroishi, T. (2014). Evolutionarily diverged regulation of X-chromosomal genes as a primal event in mouse reproductive isolation. PLoS Genet 10, e1004301.